DanQi Pill protects against heart failure through the arachidonic acid metabolism pathway by attenuating different cyclooxygenases and leukotrienes B4

BMC Complementary and Alternative Medicine

Research Article

Jing Han¹  Shuzhen Guo¹  Binghua Tang¹  Yong Wang¹  Tianjiao Shi¹  Yan Wu¹  Wei Wang¹  Qiyan Wang¹  Chun Li²  Zhongyang Liu³  Dong Li³ 

[1] Beijing University of Chinese Medicine, Bei San Huan Dong Lu, Chao Yang district, Beijing, China;Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Bei San Huan Dong Lu, Chao Yang district, Beijing, China;State Key Laboratory of Proteomics, Beijing Proteome Research Center, Institute of Radiation Medicine, Science Park Road, Beijing, China;

关键词: Gene Ontology;    Sham Group;    Model Group;    Fractional Shorten;    Panax Notoginseng;   

DOI  :  10.1186/1472-6882-14-67

 received in 2013-09-23, accepted in 2014-02-18,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundChinese herbal formulae are composed of complex components and produce comprehensive pharmacological effects. Unlike chemical drugs that have only one clear single target, the components of Chinese herbal formulae have multiple channels and targets. How to discover the pharmacological targets of Chinese herbal formulae and their underlying molecular mechanism are still under investigation.MethodsDanQi pill (DQP), which is one of the widely prescribed traditional Chinese medicines, is applied as an example drug. In this study, we used the drug target prediction model (DrugCIPHER-CS) to examine the underlying molecular mechanism of DQP, followed by experimental validation.ResultsA novel therapeutic effect pattern of DQP was identified. After determining the compounds in DQP, we used DrugCIPHER-CS to predict their potential targets. These potential targets were significantly enriched in well-known cardiovascular disease-related pathways. For example, the biological processes of neuroactive ligand–receptor interaction, calcium-signaling pathway, and aminoacyl–tRNA biosynthesis were involved. A new and significant pathway, arachidonic acid (AA) metabolism, was also identified in this study. This predicted pathway alteration was validated with an animal model of heart failure (HF). Results show that DQP had effect both on thromboxane B2 (TXB2) and Prostaglandin I2 (PGI2) in different patterns. It can down-regulate the TXB2 and up-regulate the PGI2 in diverse way. Remarkably, it also had effect on cyclooxygenase (COX)-1 and COX2 by suppressing their levels, which may be the critical and novel mechanism of cardiacprotective efficacy for DQP. Furthermore, leukotrienes B4 (LTB4) receptor, another key molecule of AA metabolism which finally mediated gastrotoxic leukotrienes, was also reduced by DQP.ConclusionsThe combination of drug target prediction and experimental validation provides new insights into the complicated mechanism of DQP.

【 授权许可】

CC BY   
© Wang et al.; licensee BioMed Central Ltd. 2014